Following a brief introduction of relaxin family members, receptors and related signalling pathways,we review effects of relaxin on cardiovascular system,particularly,its anti-fibrotic action.The heart and vessels are target organs of relaxin.Recent studies have documented that the relaxin genes are upregulated in the diseased heart of humans and experimental animals.In several animal disease models,relaxin can reverse cardiac fibrosis.Relaxin may also indirectly promote myocardial regeneration and repair by suppressing fibrotic healing.Further research needs to focus on elucidating the exact mechanisms utilized by relaxin to induce these cardiac actions and translation of experimental findings to novel therapy of cardiovascular disease.

Background Lens epithelial cells (LECs)play an important role in maintaining the lens transparency.Inflammatory cytokines have been clarified to participate in the formation of traumatic and after cataracts.However,the influence of inflammatory cytokines on the migration of LECs is still studying.Objective This study was to investigate the effects of interleukin-1 alpha (IL-1α),interleukin-1 beta (IL-lβ),IL-6,tumor necrosis factor alpha(TNF-α) and their mixture on the migration of human LECs in vitro.Methods HLE-B3 cells were cultured in DMEM containing 0.5％ fetal bovine serum.10 μg/L of IL-1α,IL-1β,IL-6,TNF-α or the mixture was added in the medium for 24 hours,respectively.Wound-scratch assay and transwell monolayer permeability assay were used to evaluate the effects of different cytokines on LECs migration.The migrating cell numbers at the scratch zone and the transmembrane cell numbers at 12:00,3:00,6:00,9:00 and the center areas on the transwell chamber were calculated under the inverted microscope.In the control group,LECs were cultured in DMEM with 0.5％ fetal bovine serum only.Results Wound-scratch assay revealed that 24 hours after cytokine incubation,the LECs numbers in the scratch zone were significantly less in the control group compared with the IL-1β group and TNF-αgroup (P =0.000,0.000),and those in the mixture group were higher than the IL-1β group and TNF-α group (P=O.000,0.000).However,no significant change was found in migrating LECs number between IL-1o group or IL-6 group and the control group (P =0.600,0.098).Transwell assay displayed that after 24-hour culture with cytokines,the largest density of transmembrane LECs was obtained in the mixture group,with a significant difference in comparison with the IL-1β group or TNF-α group (P=0.000,0.000).However,the transmembrane LECs were much more in the IL-1 β group or TNF-α group compared with the control group (P =0.000,0.000).Only a few transmembrane LECs were seen in the IL-1α group and IL-6 group in comparison with the control group(P =0.056,0.327).Conclusions IL-lα and IL-6 can not stimulate the migration of human LECs,but TNF-α and IL-1β can enhance their migration markedly.Mixture of these cytokines may play a much powerful influence on LECs migration.

According to the analysis and integration on prior research results regarding meridian essence, it is believed that high-energy metabolism is one of the main characteristics of along-meridian specificity. With discussion on the formation mechanism of along-meridians high-energy metabolism as entry point, it is found out that proteins of voltage-gated calcium channel along the meridians are likely to play an essential role of starting and coupling during the along-meridians functional activity. Thus, the hypothesis "proteins coupling in the meridians" is modified to the hypothesis "calcium channels proteins coupling in the meridians", which opens new path to reveal material basis and action mechanism of meridians.
Calcium ; metabolism ; Calcium Channels ; metabolism ; Energy Metabolism ; Humans ; Meridians

Objective To study the correlation between alopecia areata and the susceptibility genes identified in our previous study with Han Chinese population. Methods The study performed an independent replication study using 736 cases and 1 840 controls. DNA was extracted from peripheral blood leukocytes by salting out with saturat-ed NaCl solution according to standard methods. The evidence for association had been obtained from former gene study. Then a fine-mapping study and genotyped the locus with an additional 17 SNPs were performed. Data were analyzed with the use of Plink 1. 07 software. Results Only one SNP achieved nominal significance, rs3087243 (P = 0. 041, OR = 1. 18, 95% CI = 1. 01 ~ 1. 38). The other 16 genes (TLR1, DMBT1, CHIT1, GBP4, CIITA, IL31RA, CD96, INPPL1, MASP2, IL-13, KIAA0350, PTPN22, SPATA5, TRAF1 / C5, IL1A, IL2R) failed. A further stratification analysis of alopecia areata was adopted, including the analysis of family history, the age of on-set and the severity of alopecia areata. The stratification analysis revealed that the age of onset > 20 years achieved nominal significance P < 0. 05 for one SNP, rs2416808 (P = 0. 018, OR = 1. 35, 95% CI = 1. 05 ~ 1. 74), where-as, the other results were of no statistical significance. Conclusion The results indicate that 17 SNPs may not be associated with AA in Han Chinese population. Further study should be performed in a larger Han Chinese sam-ples.

Objective To study the effects of quantitative 24-hour urinary protein on the thyroid hormone levels in patients with severe preeclamp-sia,and clarify the impact of severe urinary protein on hypothyroid in severe preeclampsia patients. Methods A total of 166 patients with severe pre-eclampsia were recruited for the study and divided into mild proteinuria group(2.0-4.9 g/d),midrange group(5-10 g/d)and severe group(>10 g/d)according to the quantitative 24-hour urinary protein. 268 healthy female individuals with normal blood pressure and uric routine in the same stage of pregnancy and of the same age were selected into control group. Serum thyrotropin(TSH),free triiodothyronine(FT3)and free thyroxine (FT4)levels were determined by solid-phase chemiluminescent enzyme immunoassay method(CMIA). The thyroid peroxidase antibody(TPOAb) and thyroglobulin antibody(TGAb)concentration were detected by electrochemiluminescent assay(ECLIA). Results TSH levels were signifi-cantly higher in patients comparing to the control group(P<0.01). In addition,severe group showed higher TSH levels than mild group(P<0.01). FT4 and FT3 levels were obviously decreased with the progression of the disease(P<0.01 and P<0.05). The positive rate of TPOAb in mild group was significantly higher than that in moderate group(OR=9.8,P<0.05). There was no significant difference of the TGAb positive rate among three patient groups(P>0.05). The incidence of subclinical hypothyroidism and clinical hypothyroidism in severe group was significantly higher than that in mild group and in control group(OR=2.5,P<0.05 and OR=9.0,P<0.05;OR=8.0,P<0.01 and OR=43.4,P<0.01). Conclusion Our re-sults indicated that 24-hour urine protein in severe preeclampsia patients has extensive effects on thyroid hormones levels. With the increasing of quantitative 24-hour urinary protein,the level of TSH increased and the FT4 decreased. Thyroid autoantibody positiveness has extensive effects on 24- hour urine protein. Incidence of hypothyroid increased with the increase of quantitative 24-hour urinary protein. 24-hour urinary protein quantitative was a risk factor for hypothyroidism in severe preeclampsia patients. More attention should be paid to the monitoring of 24-hour urinary protein in se-vere preeclampsia patients.

Objective To study thyroid hormone changes in women with pre-eclampsia patients,the characteristics of thyroid disease and its relationship with pre-eclampsia.Methods From May 2011 to December 2012 171 patients with pre-eclampsia who delivered in Shengjing Hospital of China Medical University were recruited as prc-eclampsia(PE) group,among which 114 cases were defined as early onset pre-eclampsia (EP) group and 57 cases were defined as late onset pre-eclampsia (LP) group.And 171 healthy women with same age and same stage of pregnancy were selected as the control group.Their blood pressures were normal and they had no obstetrical complications.Serum thyrotropin (TSH),free triiodothyronine (FT3) and free thyroxine (FT4) levels were determined by solid-phase chemiluminescent enzyme immunoassay method (CMIA).Thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were measured by electro-chemiluminescent assay (ECLIA).The positive rate was calculated (TPOAb ＞ 5.6 U/L,TGAb ＞ 4.1 U/L were defined as positive result).The relationship between TSH,FT3,FT4 level and blood pressure was analyzed in women with pre-eclampsia.Results (1) The median values of TSH,FT4 and FT3 in PE group were 3.4 mU/L,(12.0 ± 3.0) pmol/L and(3.9 ± 0.9) pmol/L.In the control group,they were 1.9 mU/L,(13.4 ± 2.4) and (5.0 ± 1.3) pmol/L.There were statistically significant differences between the two groups(P ＜ 0.01).In EP group,the median values of TSH,FT4 and FT3 were 3.3 mU/L,(12.1 ± 3.4) pmol/L and (3.8 ± 0.9) pmol/L.The differences between EP group and the control group were statistically significant (P ＜ 0.01).In LP group,the median values of TSH,FT4 and FT3 were 3.4 mU/L,(11.9 ± 3.1) pmol/L and (3.9 ± 1.0) pmol/L.There were statistically significant differences compared to the control group(P ＜0.01).While there was no difference between EP group and LP group (P ＞ 0.05).(2) The positive rate of TPOAb and TGAb in PE group were 15.2％ (26/171)and 21.6％ (37/171),and were 12.3％ (21/171) and 14.6％ (25/171) in the control group.There was statistically significant difference in the TGAb positive rate (P ＜ 0.01),but the difference in TPOAb positive rate was not statistically different(P ＞0.05).The TPOAb positive rates in EP group and LP group were 12.3 ％ (14/114) and 21.1％ (12/57),respectively,with no statistically significant difference (P ＞ 0.05).And the positive rates of TGAb in EP group and LP group were 21.9％ (25/114)and 21.1％ (12/57),respectively,with no statistically significant difference(P ＞ 0.05).The positive rate of TPOAb in LP group and in the control group had statistically significant difference(P ＜0.01).(3) The morbidity of thyroid disease in PE group and in the control group were 47.4％ (81/171) and 16.4％ (28/171),with statistically significant difference (P ＜ 0.01).(4) The morbidity of subclinical hypothyroidism or hypothyroidism in PE group and in the control group were 45.0％ (77/171) and 16.4％ (28/171),with statistically significant difference(P ＜0.01).(5) The morbidity of subclinical hyperthyroidism in PE group and in the control group were 2.3 ％ (4/171) and 1.8 ％ (3/171),with no statistically significant difference (P＞0.05).(6) In PE group,women with TSH level of 0.3-3.3 mU/L had systolic pressure of(170 ± 21)mmHg (1mmHg =0.133 kPa)and diastolic pressure of(112 ± 15) mmHg; women with TSH ＞ 3.3 mU/L had systolic pressure of(166 ± 21)mmHg and diastolic pressure of(109 ± 13)mmHg.There was no statistically significant difference(P ＞ 0.05).But the diastolic pressure in EP group and LP group had statistically significant difference(P ＜ 0.01).In PE group,no correlation was found among TSH,FT4 levels and systolic pressure,diastolic pressure(P ＞ 0.05).FT3 level was negatively correlated to diastolic pressure (r =-0.172,P =0.023).Conclusions It is common that pre-eclampsia is complicated with thyroid dysfunction,mainly subclinical hypothyroidism.Thus it is nessesary to test thyroid hormone and thyroid antibodies in women with pre-eclampsia.The decrease of FT3 and FT4,the increase of TSH and the presence of TPOAb and TGAb are related with the presence of pre-eclampsia.

Abstract?AIM: To investigate the influence of propylene glycol mannite sulfate ( PGMS ) on the expression of tumor necrosis factor -α( TNF-α) and interleukin-1β( IL-1β) , in diabetic retinopathy by a rat model, to study the mechanism of PGMS against diabetic retinopathy, and provide a reliable theoretical and experimental evidence for the PGMS to be applied to clinical prevention and treatment of diabetic retinopathy.?METHODS: Male Wistar rats were randomized into 4 groups, normal control group, diabetic control group and PGMS in group, the PGMS in groups included the doses of 50mg/kg and 100mg/kg. 1% streptozotocin ( STZ) of 60 mg/kg was intraperitoneally injected in rats to establish the diabetic models. The PGMS with the doses of 50mg/kg and 100mg/kg were used to gavage in different groups of models for 12wk.Twelve weeks later, the animals were sacrificed and retinas were isolated. The aqueous humors and serums were taken, expressions of TNF-αand IL-1βprotein in retinas, aqueous humors and serums were detected by enzyme-linked immunosorbent assay ( ELISA) , respectively.The location and the expression of TNF-αand IL-1βprotein in retina tissue was detected by immunohistochemistry.?RESULTS: Twelve weeks after the use of PGMS, the level of blood glucose was not changed.ELISA showed that the expression of TNF-αand IL-1βprotein in serum and retina was significantly increased in diabetic control group than in normal control group(P<0.05), but in the groups which PGMS was given reduced, lower than those in diabetes mellitus( DM) group, especially as the concentration of PGMS increased ( P<0.05 ).But the levels of aqueous humor's TNF-αand IL-1βproteins in PGMS group were not reduced.Immunohistochemistry showed that the TNF -α protein was almost not expressed in normal control group. But the TNF-αprotein was highly expressed in diabetic control group. The expression mainly located in the ganglion cell layer, the inner plexiform layer, outer plexiform layer and pigment epithelium. The TNF-αprotein was weakly expressed at the group of 50mg/kg PGMS, the TNF-αprotein was almost not expressed at the group of 100mg/kg PGMS.When the normal control group was detected, the IL-1βprotein was weakly expressed in the outer plexiform layer.But the IL-1βprotein was also highly expressed in diabetic control group.The expression mainly located in the inner plexiform layer, outer plexiform layer and pigment epithelium. The IL -1βprotein was weakly expressed at the group of 50mg/kg and 100mg/kg PGMS.?CONCLUSION:PGMS can treat the diabetic retinopathy by downregulating the expressions of TNF-αand IL-1βin early diabetic retinopathy.PGMS maybe have a good control effect on early diabetic retinopathy.

Objective To observe the activation of anti-viral innate immune response of type Ⅰinterferon and inhibition of hepatitis B virus (HBV)genome replication in mice by HBV-3p-siRNA. Methods HBV-3p-siRNA was designed by targeting specific sequence of HBV S/P mRNA and was generated by in vitro transcription.Negative control siRNA (NC-siRNA)and non-modified HBV-siRNA were used as control groups.Blood samples were collected from tail vein of mice and the model of HBV-infected mice were established by hydrodynamic injection.Forty mice were divided into 4 groups with 10 in each group.The model group was only injected with pGL3.0-HBV1 .2 copy plasmid.The negative control group received peritoneal injection of NC-siRNA.HBV-siRNA group received peritoneal injection of HBV-siRNA and HBV-3p-siRNA group received peritoneal injection of HBV-3p-siRNA.The interferon-β(IFN-β)and hepatitis B surface antigen (HBsAg)in serum were detected by enzyme linked immunosorbent assay (ELISA).The copies of HBV DNA were assessed by fluore scence quantitative polymerase chain reaction (PCR ).The statistical difference between groups was determined using One way-ANOVA analysis by LSD or Dunnett T3.Results Serum level of IFN-β was (12.37±5 .32)pg/mL in model group,(22.61 ±6.29 )pg/mL in negative control group,(26.40±5 .39)pg/mL in HBV-siRNA group and (68.37± 21 .00 ) pg/mL in HBV-3p-siRNA group.The secretions of IFN-β into serum were significantly enhanced by HBV-siRNA and HBV-3p-siRNA compared with model group (F =23.988 and 46.523,respectively,both P <0.01).Serum level of HBsAg was (2 864.86±907.11 )ng/mL in model group,(2 198.86±456.89 )ng/mL in negative control group,(1 049.71 ± 396.28 )ng/mL in HBV-siRNA group and (640.86±383.08)ng/mL in HBV-3p-siRNA group.The expressions of HBsAg were inhibited by HBV-3p-siRNA and HBV-siRNA compared with model group (F = 23.537 and 39.144, respectively;P =0.025 and 0.010,respectively).Serum level of HBV DNA was (2.54 ×104 ±1 .46 × 104 )copy/mL in model group,(2.22×104 ±2.62×103 )copy/mL in negative control group,(3.59×103 ±2.88×103 )copy/mL in HBV-siRNA group and (2.65 ×103 ±1 .46×103 )copy/mL in HBV-3p-siRNA group.Serum level of HBV DNA were inhibited by HBV-3p-siRNA and HBV-siRNA compared with model group (F =15 .013 and 16.741 ,respectively,both P <0.05 ).All of the indicated siRNA used in the experiments showed no apparent effects on the body mass index of the mice models.Conclusion HBV-3p-siRNA,which induces the production of IFN-β and inhibits HBV replication through gene silencing in vivo ,may be a powerful bifunctional antiviral molecule.

Objective:To evaluate the benefit of autologous stem cell transplantation (ASCT) as a consolidation therapy in the survival of multiple myeloma (MM) patients at different risks. Methods:A total of 67 MM patients who received ASCT as consolida-tion therapy between August 2006 and July 2011 were enrolled in the retrospective study. The cases were divided into three risk groups on the basis of the International Staging System and fluorescence in situ hybridization. Another 67 patients who accepted consolidation chemotherapy at the same period were selected as case-paired controls matched in terms of age, sex, optimal response after induction, and risk stratifications. All the patients received bortezomib-and/or thalidomide-based induction therapies. Results:No statistical differ-ences in non-complete remission (nCR)/complete remission (CR) rate were observed between the ASCT and chemotherapy groups (44.8%vs. 37.3%, P=0.380) after the induction therapy. The progression-free survival (PFS) was longer in the ASCT group than in the chemotherapy group (32.4 months vs. 15.1 months, P<0.001). The overall survival (OS) was longer in the ASCT group than in the che-motherapy group (58.8 months vs. 42.1 months, P=0.009). both the PFS (median:30.5 months vs. 11.2 months, P<0.001) and the OS (median:85.5 months vs. 34 months, P=0.015) rates were significantly prolonged in the high-risk subgroup after ASCT. In the interme-diate-risk subgroup, neither PFS nor OS showed any significance after ASCT (P>0.05). In the low-risk subgroup, only PFS was extend-ed (median: 34.8 months vs. 17.6 months, P=0.012) after ASCT, without significant improvements in the OS (P>0.05). Conclusion:The MM patients obtained cytogenetic high-risk benefits mostly from ASCT consolidation after inductions based on novel agents.

Objective To study effects of different degree of hypothyroidism in severe preeclampsia (S-PE) pregnant women on renal function and the correlation between them.Methods 46 S-PE patients with subclinical hypothyroidism (SCH) registered for treatment in the Shengjing Hospital of China Medical University from May 2011 to March 2013 were selected into SCH group,and 23 S-PE with overt hypothyroidism (OH) were selected into OH group,and 109 S-PE with normal thyroid stimulating hormone (TSH) levels were selected into simple group.Thyroid hormone and kidney function tests were analyzed in pregnant women with S-PE.We made an analysis of the relative risk of the detection rate of abnormal renal function and also the relationship between the levels of thyroid hormone and serum uric acid,serum urea and creatinine in patients with S-PE.Results (1) In SCH group serum TSH was (6.1±3.2) mU/L,free triiodothyronine (FT3) was (4.0±0.6) pmol/L,free thyroxine (FT4) was (11.8± 1.5) pmol/L; in OH group serum TSH was (5.2± 1.3) mU/L,FT3 was (3.7±0.6) pmol/L,FT4 was (9.3±0.5) pmol/L; in simple S-PE group serum TSH was (1.9±0.8) mU/L,FT3 was (4.0±0.8) pmol/L and FT4 was (11.9±1.9) pmol/L.TSH in SCH group was significantly higher than that in simple S-PE group (P＞0.01),the difference of in SCH and OH group were not statistically significant (P＞0.05).The difference of FT3 in three groups were not statistically significant (P＜0.05) ;FT4 in OH group was significantly lower than thoes in SCH and simple groups (P＜0.05).(2)Serum uric acid,creatinine and urea levels in OH group was (436± 114),(75± 15) μmol/L and (6±3)mmol/L,in simple S-PE group they were (378± 114),(65 ±22) μmol/L and (5±3) mmol/L.In comparison,the differences was statistically significant(P＜0.05).The differences were not statistically significant in SCH and OH groups (P＞0.05).(3)The abnormal detection rate of uric acid was significantly higher in SCH than that in OH group [46％ (21/46) versus 22％ (5/23),OR=3.0,P＜0.05].The comparison of remaining index has no statistical significance(P＞0.05).(4)In SCH group there was a significant inverse correlation of serum FT3 with serum urea levels,serum creatinine and serum uric acid (r=-0.32,-0.58,-0.35,P＜0.05).There was not a correlation of serum TSH,FT4 with indicators of renal function (P＞0.05).In OH group there was a negative correlation between FT3 and serum creatinine concentrations (r=-0.40,P＜0.05).In OH group there was not a correlation of FT3 with serum uric acid and urea (P＞0.05).There was a positive correlation between TSH and serum creatinine in simple S-PE group (r=0.20,P=0.04).There was not a correlation between TSH and serum urea(r=0.04,P=0.65),and serum uric acid (r=0.12,P=0.20).Conclusions There was effect of different hypothyrosis state in pre-eclampsia patients on renal function.Serum uric acid,urea and creatinine concentrations in S-PE pregnant women with OH were significantly higher than those in simple S-PE group with normal TSH.There was a negative correlation between FT3 and serum creatinine in S-PE.Hence the thyroid function should be regularly monitored in S-PE patients to find damage of renal function and management hypothyrosis.